The latest round of industrial action and rallies comes as trade unions continue to pile pressure on Macron to try force him to backtrack on his reforms of the railways and the wider public sector.
The state railway operator SNCF said the fourth instalment of the strikes that began earlier this month would heavily disrupt services on Wednesday and Thursday, with just one in three high-speed TGVs running.
Only one in four regional inter-city trains and one in three trains to Switzerland will operate.
Eurostar services to London will be only marginally affected however, with four out of five trains set to run as announced.
Lawmakers in the lower house of parliament late Tuesday voted overwhelmingly in favour of a reform of the train network which will erode railway workers' privileges and change the status of the SNCF.
After Tuesday's vote of 454 to 80 in the National Assembly, the legislation, which is backed by Macron's own party and the centre-right opposition, moves to the Senate.
Macron is hoping that the law will be passed quickly, undermining the rolling strikes which are scheduled until the end of June.
He is largely backed by public opinion, with 61 percent of respondents to a recent Ifop poll saying they wanted the government to push through the reforms.
But trade unions have vowed to continue their fight.
They have called for a day of nationwide work stoppages and demonstrations Thursday as part of their efforts to mobilise various groups opposed to Macron's reforms.
Civil servants, workers in state retirement homes and students have all been called to join protests that could bring hundreds of thousands of people onto the street.
Around 300,000 civil servants, rail workers and students took part in the last day of anti-Macron demonstrations on March 22, according to police figures.
Macron, who sees his own credibility as a reformer on the line as he prepares to mark the first anniversary of his presidency on May 14, has insisted he will not back down.
Once passed by the lower house the rail reform law will proceed to the Senate where it will not be examined before May 29.