Heidi Allen, Anna Soubry and Sarah Wollaston hit out at Theresa May’s “disastrous” handling of Brexit as they quit.

The three - who will join the eight ex-Labour MPs who have formed the Independent Group (TIG) - claimed Mrs May had failed to stand up to the “hard line” European Research Group (ERG) of Brexiteers.

The move poses a fresh headache for Mrs May as she prepared to face Prime Minister’s Questions in the Commons before heading to Brussels for Brexit talks with Jean-Claude Juncker.

MP Anna Soubry has resigned from the Conservative party

In a letter to Mrs May, the three MPs said: “We no longer feel we can remain in the party of a Government whose policies and priorities are so firmly in the grip of the ERG and DUP.

“Brexit has re-defined the Conservative Party - undoing all the efforts to modernise it. There has been a dismal failure to stand up to the hard line ERG which operates openly as a party within a party, with its own leader, whip and policy.”

They added: “The final straw for us has been this Government’s disastrous handling of Brexit.”

The prime minister said she was “saddened” by the resignations.

In a statement, Mrs May said: “These are people who have given dedicated service to our party over many years, and I thank them for it.

“Of course, the UK’s membership of the EU has been a source of disagreement both in our party and our country for a long time.

“Ending that membership after four decades was never going to be easy.

“But by delivering on our manifesto commitment and implementing the decision of the British people we are doing the right thing for our country.

“And in doing so, we can move forward together towards a brighter future.”

Veteran former Cabinet minister Ken Clarke, a leading Europhile on the Tory benches, suggested as many as six Conservatives could eventually split away.

He told the Press Association: “I can think of half a dozen who I’m sure will contemplate it unless our party changes its direction.”

Mr Clarke said he was a “lifelong Conservative” but younger members would “have to consider long term whether they can continue to associate with a party that at the moment is so much dominated by its extreme right wing”.

Ms Ryan’s decision to quit Labour followed the launch of TIG on Monday by seven of her colleagues.

The Enfield North MP, who chaired Labour Friends of Israel, said the Labour leader had ignored calls to tackle the problem and was not fit to be prime minister.

“We never had this problem in the party before he was the leader. It comes with him, it is part of his politics, I am afraid,” she told Today.

“He has introduced or allowed to happen in our party this scourge of anti-Semitism. It has completely infected the party and at every opportunity to deal with it he has not done so.

“We have had a whitewash report, we have had unprecedented actions of Jewish people feeling they have to demonstrate against the Labour Party in Parliament Square.

“We have had endless calls on him to deal with the most virulent, vile anti-Semitism - bullying, abuse and aggression - and he has turned away from doing that.”

Ms Ryan, who has represented Enfield North since 1997, with a break from 2010-15, and served as a minister in Tony Blair’s government, also attacked Mr Corbyn’s position on the EU.

“The other huge problem is that I think Jeremy Corbyn is aiding and abetting a hard Brexit,” she said.

Meanwhile, Labour launched a consultation on changes to allow voters to force MPs to seek re-election if they swap parties.

The proposed right to recall comes after the launch on Monday of the Independent Group by seven ex-Labour MPs including former shadow ministers Chuka Umunna, Luciana Berger and Chris Leslie.

Members of the new group have indicated they will resist demands from the leadership, including shadow chancellor John McDonnell, to step down and seek a fresh mandate from voters in a by-election.

Ms Ryan said a “large number” of Labour MPs are unhappy with the leadership and she hoped there will be further defections to the Independent Group - including from other parties.

“I hope that all like-minded MPs from whatever party will want to join this group. It is early days. It is about trying to change the political weather,” she said.

With a poll taken the day after the Independent Group’s launch putting the breakaway MPs on 10% support to Labour’s 26% nationally, Mr Corbyn’s party would be hopeful of seizing back most if not all of the seats in by-election contests.

Although the Independent MPs may benefit from some personal support, all of their constituencies - with the exception of Angela Smith’s Penistone and Stocksbridge and Ms Ryan’s Enfield North - are rock-solid Labour seats which would need a substantial swing to change hands.

In an indication that Labour expects to hold on to much of its support in any by-election, party sources said one of the key reasons for allowing recall when an MP crosses the floor is because people cast their vote primarily for the party and its platform rather than the candidate.

At present, recall petitions can only be launched in a handful of circumstances, such as a serious breach of parliamentary rules or a criminal conviction. A by-election is forced if the petition is signed by 10% of constituents - usually around 7,000 people - within six weeks.

Labour will consult on extending the principle to cover MPs who switch political allegiance.

Shadow Cabinet Office minister Jon Trickett said: “Power comes from the people but for too long the overwhelming majority have been shut out. That’s why trust in politics and in elites is rightly falling.

“Communities should not have to wait for up to five years to act if they feel their MP is not properly representing their interests, especially with the restrictions of the Fixed Term Parliament Act.

“This proposed reform has the dramatic potential to empower citizens and will be one of many measures the Labour Party is planning to consult on and announce that will change the way politics in this country is done.”

Three Conservative MPs quit party to join breakaway group of former Labour MPs