At least 41 of the dead were inside the charter bus, which was carrying a group of mostly elderly people on a day trip Friday to the Basque region, authorities said. But authorities were still trying to determine the identities of the victims, prosecutor Christophe Auger said, and it was possible the passenger list was lost in the fire, he said.
The driver of the truck and his 3-year-old son also were killed, Auger said.
Eight people survived the wreck on the winding, narrow two-lane highway that runs through French wine country. The bus was left a charred frame.
In a statement, President François Hollande called the accident "a great tragedy." He said the relatives of the victims could be assured of "the solidarity of the whole nation."
The Prime Minister, the minister of interior and transport secretary of state arrived at the scene with promises of a prompt investigation.
Hollande's office said he will travel to Petit-Palais, the hometown for most of the victims, Tuesday morning to take part in a tribute.
Head-on crash on a narrow road
The crash happened at 7:30 a.m. on a wooded portion of the D17 highway in Puisseguin, near Bordeaux in southern France.
The bus began its trip in Petit-Palais 15 minutes earlier, according to Jean-Claude Leonardet, 73, who suffered a head injury as he escaped with his wife.
Authorities said the full tank of gas on the bus contributed to the size of the fire.
Alain Vidalies, the secretary of state for transport, told the public radio station France Info he did not believe the condition of the road was a factor. The road was repaved in 2011 and was in good condition, he said.
Puisseguin Mayor Xavier Sublett said on French radio and TV that the bus driver, who survived the crash, saved lives by opening the doors to let people escape.
"If the doors would not have been opened, we would all have perished," said Leonardet.
He told CNN affiliate BFMTV
he assisted the driver in getting another person out of the bus, and that the driver of a car behind the bus also helped rescue passengers.
Identification of victims
Authorities said they were not ready to release the names of the victims because the charred bodies made identification difficult.
"The identification process will be done following analysis from what we collect and ... we will probably be able to return the bodies to the families within three weeks," Gendarmerie Deputy Director of Criminal Research, Patrick Touron, said at the crash site.
He said the black boxes are "seriously damaged" and will have to be sent to "the correct experts so as to extract information."