The use of zwitterionic copolymers for the design of fouling resistant membranes by in-situ modification remains unexplored because these copolymers face solubility issues when blended with common hydrophobic membrane materials such as poly(vinylidene fluoride) (PVDF). Here, we overcame this issue using a copolymer of 2-methacryloyloxyethyl phosphorylcholine and methacryloyloxyethyl butylurethane groups, named PMBU. The resulting membranes formed by vapor-induced phase separation exhibited a highly porous (porosity of 75%) and strong (modulus of elasticity E > 80 MPa) bi-continuous structure, while the virgin PVDF membrane still contained nodules, resulting in weaker membrane (E = 67 MPa). ATR FT-IR in local and mapping modes evidenced a strong signal ascribed to the presence of ester groups of PMBU at 1730 cm(-1,) fairly well distributed at the surface of the membranes. It led to a significant improvement of their hydrophilic properties with a hydration capacity reaching 280 mg/cm(3). Consequently, the modified membranes showed excellent antifouling properties when contacted with bacterial solutions (Escherichia coli) and totally inhibited biofouling by whole blood. Furthermore, a flux recovery ratio of 42% was measured with the best membrane after 4 water/humic acid filtration cycles, while it was 17% in the same conditions with a commercial hydrophilic PVDF membrane. Hence this work demonstrates that fouling-resistant zwitterionic bi-continuous PVDF-based membranes can be prepared by in-situ modification.