Olympic 50m champion in London in 2012 and silver medalist in Rio in 2016, Manaudou (30) will headline French swimming in Tokyo (23 July-8 August).
Manaudou won in 21 sec 72 Friday, for 21 sec 80 set as minimum by the tricolor supervision.
He had already swam 21 sec 73 last December, at the French Championships in Saint-Raphaël.
No French swimmer has done better throughout this first qualifying window which formally closes Sunday evening at the end of the Marseille meeting.
The younger brother of Laure Manaudou, in his thirties since last November, returned to swimming two years ago with the ambition to win back Olympic gold in the 50m, after more than two and a half years away from the pools, the after JO-2016 in spring 2019, spent in particular playing handball.
In the Marseilles basin, Manaudou only swam on Friday his ninth and tenths 50m long course since his return.
He had dominated the morning series in 21 sec 87.
Auspicious four months from the Tokyo Olympics
Four months before the Tokyo Games, his best performance since he plunged again remains his 21 56 sec swims in January 2020 at the Luxembourg meeting, a good distance from his personal best (21.19 in 2015).
For comparison, he was crowned Olympic champion in 21 sec 34 nine years ago.
And the Olympic podium was played in 21 sec 4 / 10ths four years later.
In addition to the first wave of qualifiers - which Manaudou is the first to integrate - which will take shape by Sunday, the last sesames will be distributed in a second time at the 2021 French Championships, mid-June in Chartres, according to minimum timing less records, and within the limit of two qualifiers per race.
Florent Manaudou: "I have to work"