This study aimed at examining the performance of the ballasted flocculation unit (BFU) on treating combined sewer overflows (CSO). Hence, the full-scale BFU at the largest wastewater treatment plant in Europe (Seine Aval plant near Paris, France) is investigated during three sampling campaigns. Of the 97 molecules targeted, 57 substances including 18 priority substances were detected in the BFU influents confirming that CSO treatment has definitively proven to be necessary. On operating at the optimal chemical and sand doses, ballasted flocculation appears to be a suitable technology to remove particles, carbonaceous and phosphorous pollutants, particulate metals and most of hydrophobic organic compounds whilst nitrogenous pollutants and most of hydrophilic compounds are from poorly (< 20%) to moderately (< 50%) removed. The BFU appeared less sensitive to the influent concentration fluctuations and hydraulic peak load (at the scale of the campaigns considered) than to the adjustments of chemical doses and sand injection.