A fourth person is in hospital with life-threatening injuries after the crash, which occurred near Waltham Abbey around 6.15pm on Monday and caused lengthy traffic delays.
Essex Police said in a statement the collision occurred between junctions 27 and 26 of the anti-clockwise carriageway, with two drivers arrested on suspicion of causing death and serious injury by dangerous driving.
The M25 was closed between those two junctions for some 11 hours, with Highways England tweeting soon after 5am that it had reopened.
Police said they were eager to trace the movements of all three vehicles – a Ford Mondeo, a minibus and a lorry – leading up to the collision.
They are urging witnesses with dashcam footage to submit a report or call 101 citing incident 972 of Monday, August 23.
Information can also be given to Crimestoppers anonymously on 0800 555 111.
Detective Sergeant Steve Holmes, from the Serious Collision Investigation Unit, said: “This evening has been incredibly challenging and we are continuing to work as quickly as we can to piece together exactly what led to this tragic incident.
“My thoughts, and those of all officers on scene, are with the families of those who lost their lives this evening.
“At present, two drivers have been arrested on suspicion of causing death by dangerous driving and on suspicion of causing serious injury by dangerous driving.
“I need anyone with further information to come forward.”
Emergency services have also thanked motorists for their patience in the face of delays of several hours due to the collision, which was attended by nine ambulances, two air ambulances, several police vehicles and fire engines from Brentwood, Loughton, Waltham Abbey and Epping.
Parv Domah was among those caught up in the traffic tailbacks near junction 26.
He told the PA news agency last night: “I can’t tell you exactly what happened, I can only say I’ve been here going on three hours.
“There were approximately 30 emergency vehicles that drove past in that time, as well as two air ambulances.
“Traffic was stopped on both sides of the carriageway at one point and now on the anti-clockwise is still shut.”