Abstract Background Interval cancer (IC) is a critical issue in colorectal cancer (CRC) screening. We identified factors associated with ICs after faecal immunochemical test (FIT) screening and explored the impact of lowering FIT cut-off or shortening screening interval on FIT-ICs in Flanders. Methods FIT participants diagnosed with a CRC during 2013–2018 were included. Factors associated with FIT-ICs were identified using logistic regression. Distributions of FIT results among FIT-ICs were examined. Results In total, 10,122 screen-detected CRCs and 1534 FIT-ICs were included (FIT-IC proportion of 13%). FIT-ICs occurred more frequently in women (OR 1.58 [95% CI 1.41–1.76]) and ages 70–74 (OR 1.35 [1.14–1.59]). FIT-ICs were more often right-sided (OR 3.53 [2.98–4.20]), advanced stage (stage IV: OR 7.15 [5.76–8.88]), and high grade (poorly/undifferentiated: OR 2.57 [2.08–3.18]). The majority (83–92%) of FIT-ICs would still be missed if FIT cut-off was lowered from 15 to 10 µg Hb/g or screening interval was shortened from 2 to 1 year. Conclusions FIT-ICs were more common in women, older age, right-sided location, advanced stage and high grade. In Flanders, lowering FIT cut-off (to 10 µg Hb/g) or shortening screening interval (to 1 year) would have a minimal impact on FIT-ICs.