Since Monday, the Rhone valley and coastal Marseilles received up to 200mm of rain. The eastern city of Lyon saw 100mm of rain in just 24 hours, the most intense in half a century.
Meteo France, the nation's weather bureau, issued a high-level warning for the two regions, saying rains and high winds were expected to continue until Thursday.
More than 5000 people were evacuated from their homes in the southeast and east of the country.
The government asked schools in the region to close while roads and 15,000 telephone lines were cut and about a dozen night trains were cancelled.
Two nuclear power plants were also closed on Tuesday.
Prime Minister Jean-Pierre Raffarin called an emergency crisis meeting on Tuesday evening and Environment Minister Roselyne Bachelot announced she would visit Marseilles, where the governor said his emergency services were on a "war footing".
A crisis management centre - run by officials from the interior, health, transport, defence and environment ministries - has been set up in Paris to coordinate rescue operations.
Twenty-four people were killed in
floods over a year ago
Three people drowned in the Marseilles region. A man was found trapped in a flooded underground tunnel, another fell into a raging river in nearby Orange and a woman was swept away while trying to drive onto a bridge.
Police were looking for two people reported missing near Marseilles and Lyon who were thought to have drowned, but it was not clear if these were included in the toll.
Meteo France said the weather conditions were extremely worrying and would continue to be so until Thursday morning. Storms and floods killed 24 people in France just over a year ago.
Two nuclear reactors in the Ardeche region north of Marseilles were shut down because there were large quantities of clogging plant matter in the water that served to cool the plants, state power company Electricite de France said.
Most of the rivers in the region were close to bursting their banks, including the Rhone, which was raging at a critical 10,000 cubic metres per second.
About 800 people were evacuated from L'Ardoise village in the Gard department due to the threat of flooding from the Rhone on Wednesday, rescue services said.
A helicopter was due to fly over the river to examine the state of dikes, as more rain was expected to fall in the region.
Local authorities said at least 33 roads were cut, including at least one major motorway, and traffic was disrupted on several rail lines.
In the western Loire region, trains were requisitioned to transport trapped residents and motorists.
Officials warned that sporadic blackouts were possible.