Again the 21-year-old was teed up by a strong effort from his FDJ team-mates, allowing him to blast past Kenny Van Hummel (Vacansoleil-DCM) and Ramon Sinkeldam (Argos-Shimano) for victory.
The 178.2km stage featured cobbled parts and some trickier terrain than the opening day, prompting Evaldas Siskevicius (Sojasun) to make an early breakaway. Florian Vachon (Bretagne), Flavien Dassonville (BigMat-Auber 93) and Yves Lampaert (Topsport Vlaanderen) joined him to race at the front, but the peloton never allowed them to escape to more than a couple of minutes up the road.
The break was caught on the cobbles, although Julien El Fares (Sojasun) then made a move of his own, joined by Rudy Kowalski (Roubaix Lille Metropole).
With 18km remaining, however, they were reeled back in, making the sprint inevitable.
FDJ were in control of the peloton and despite Vacansoleil moving ahead, Demare made his move 200m from the line, taking a 10-second lead via time bonuses in the general classification.
The five-day race finishes back in Dunkerque on Sunday.