Despite free colorectal cancer screening in France, participation remains low and low socioeconomic status is associated with a low participation. Our aim was to assess the effect of a screening navigation program on participation and the reduction in social inequalities in a national-level organized mass screening program for colorectal cancer by fecal-occult blood test (FOBT). A multicenter (3 French departments) cluster randomized controlled trial was conducted over two years. The cluster was a small geographical unit stratified according to a deprivation index and the place of residence. A total of 14,556 subjects (72 clusters) were included in the control arm where the FOBT program involved the usual postal reminders, and 14,373 subjects (66 clusters) were included in the intervention arm. Intervention concerned only non-attended subjects with a phone number available defined as the navigable population. A screening navigator was added to the usual screening organization to identify and eliminate barriers to CRC screening with personalized contact. The participation rate by strata increased in the intervention arm. The increase was greater in affluent strata than in deprived ones. Multivariate analyses demonstrated that the intervention mainly with phone navigation increased individual participation (OR=1.19 [1.10, 1.29]) in the navigable population. For such interventions to reduce social inequalities in a country with a national level organized mass screening program, they should first be administered to deprived populations, in accordance with the principle of proportionate universalism. ClinicalTrials.gov Identifier: NCT01555450.