Christophe Auger, the prosecutor for Libourne in southwest Frances wine region, said its impossible at this stage to say why the tourist bus and the empty truck crashed on a winding road near the village of Puisseguin, 50km east of Bordeaux.
However, witnesses said the bus driver told them the truck had jackknifed and he had been unable to avoid the collision.
The crash killed 41 bus passengers, mostly elderly pensioners on a day trip, as well as the truck driver and his three-year-old son, who was riding in the truck with his father. Four other people were badly injured.
Auger said investigators top priority in the coming days is to identify the victims, a task made difficult by the charred state of their remains.
Experts expect it will take three weeks before all victims are identified.
Images on French television showed the carcass of the bus a collapsing, charred frame engulfed by smoke near Puisseguin, its seats nothing but empty metal frames.
Eight people, including the driver, escaped after the driver opened the bus door, but others were trapped as flames quickly consumed the vehicles, Puisseguin Mayor Xavier Sublett told i-Tele television.