The industrial action, which will begin at 7pm on Tuesday and end on Thursday morning at 8am, will see services cancelled throughout the country.
The four unions representing workers from France's rail operator SNCF – the CGT, CFDT, Sud and Unsa - jointly called for the one-day strike.
They are demanding the recruitment of more staff, a rise in salaries and guarantees about improvements in work conditions.
It is the first time the four unions - normally divided over the questions around rail reform - have joined forces for a protest since June 2013, when only four out of every ten trains were running.
And rail chiefs are expecting severe disruption once again with SNCF advising passengers to cancel or delay their journey if possible.
“It will be a landmark day,” said Thierry Nier, spokesman of the CGT-Cheminots union, who expects a huge mobilization of workers.
“We are down to the bare bones. Even among management discontent is on the rise,” he said.
One of the worst hit areas will be the Ile-de-France area around Paris, where SNCF chiefs predict that only one third of trains will be running.
RER services around the Ile-de-France region will be severely disrupted.
In particular passengers should note that on the RER B, which links the centre of Paris to the city's two airports Charles de Gaulle and Orly, only 50 percent of the normal services will be running.
Although staff from RATP, which runs the Paris Metro system, are also expected to join the walk-out, services on the city's underground network are expected to run almost as normal.
The Eurostar services between Paris and London will also be affected by the strike with 20 percent of services expected to be cancelled.
As for TGV services, only one in three of the usual services will operate out of Paris to the north of the country and the Atlantic coast. And it will be the same for TGV services linking cities in the south east of the country.
In the East of the country, only 50 percent of TGV services will operate.
On the TGV low cost service Ouigo, 60 percent of services will be cancelled and only 30 percent of the regional Intercité services will run and none at all will operate at night.
International train services to Italy and Spain will also be affected.
To find out if your train has been cancelled by the strike, you can CLICK HERE.