We assessed whether familial colorectal cancer (FCRC) surveillance in individuals without hereditary CRC can be optimized METHODS: The ASCCA-FCRC model simulates CRC development in individuals with a family history of CRC at 2-fold and 4-fold increased CRC risk compared to the general population. We simulated a strategy without surveillance, the current Dutch guideline (5-yearly colonoscopy between 45-75), and three sets of alternative strategies; colonoscopy surveillance, surveillance combining colonoscopy and fecal immunochemical test (FIT) and FIT-based surveillance. Each set included a range of strategies differing in age range and test interval. The optimal strategy was defined as the strategy with highest quality-adjusted life years (QALYs) satisfying all criteria: 1) in the (near-)efficiency area of the cost-effectiveness frontier, and compared to current surveillance 2) non-inferior effectiveness, 3) no substantial increase in colonoscopy burden and, 4) not more expensive. The optimal strategy was 10-yearly colonoscopy with 2-yearly FIT between colonoscopies from age 40 to 80 for both 2- and 4-fold increased CRC risk. At 2-fold risk, this strategy prevented 0.8 more CRC deaths, gained 15.8 more QALYs at 731 fewer colonoscopies and saved €98k over the lifetime of 1,000 individuals compared to current surveillance. At 4-fold risk, figures were 2.1 more CRC deaths prevented, 37.0 more QALYs gained at 567 fewer colonoscopies and €127k lower costs. Current surveillance was not (near-)efficient. FIT could play an important role in FCRC surveillance. Surveillance with 10-yearly colonoscopy and 2-yearly FIT between colonoscopies from age 40 to 80 increases QALYs and reduces colonoscopy burden and costs compared to current FCRC surveillance.