Another eight people were injured in the collision on a country road near Puisseguin in the Gironde region about 60km (35 miles) east of Bordeaux, the local prefect’s office said in a statement.
The bus was carrying about 50 pensioners south to the Bearn region from their homes in the village of Petit Palais and surrounding hamlets, all just a few kilometers away from the crash site, said officials.
A grainy photo on BFMTV showed smoke rising from the burnt out shell of the bus on a narrow, forested bend.
A spokesman for the interior ministry said that, as far as he could tell, all the passengers were French and from the region.
President Francois Hollande, speaking on a visit to Athens, said he had been “plunged into sadness by the tragedy” and Prime Minister Manuel Valls and other ministers were heading to the crash site.
It was the most deadly road accident in France since 53 people, mostly children, died in a bus crash in Burgundy in July 1982, according to the independent road safety organization Association Prevention Routiere.
Stricter road regulation and lower speed limits followed, and road deaths in France have fallen steeply since. According to official statistics, more than 16,000 people were dying on the roads every year in the early 1970s. In recent years the death toll has fallen below 4,000.