The two students, one described as in a life-threatening condition and another in a serious condition, were airlifted to hospital from the crash site on the A39 motorway at Lons-le-Saunier.
A further ten students and one member of staff from Cheltenham Bournside School received minor injuries.
There were 42 students, six staff and two drivers on board at the time.
A school spokesman said: “We were deeply saddened to hear of a serious incident involving the coach taking our students to Dora Baltea earlier today. Our hearts go out to all those involved.
“Two of the students were airlifted to hospital, one in a life-threatening condition and another in a serious condition.
“The school have met with the parents of these two students, who are now on their way to France to be with their children.”
Operated by Caernarfon-based Express Motors, the coach had left the UK yesterday and was making its way to Italy for a week’s camping trip.
The statement from the school said the remaining students and staff were with police.
It said: “We are currently in the process of liaising with the Global Response Centre (Foreign and Commonwealth Office) and the trip organiser, with regard to how and when students will be returning to the UK.
“When we have any further information, it will be shared with parents concerned.”
A Foreign Office spokesman said: “We are providing support to a group of British nationals following a coach crash in France. We are in contact with the relevant local authorities.”