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Background Regular faecal immunochemical test (FIT) screening reduces CRC incidence and mortality; however, both initial uptake and longitudinal adherence rates remain suboptimal worldwide. Our previous two randomized controlled trials (RCTs) have demonstrated the effectiveness of the Health Belief Model (HBM)-based WhatsApp chatbot in improving both rates when compared to a standard text reminder.We aimed to provide qualitative evidence about the profile of reasons for initial screening uptake and longitudinal adherence to CRC screening.Methods Eight callback focus-group interviews using semi-structural protocols were conducted among 49 participants (mean age = 63.02, 32 females), who received HBM-based interventions in the two previous RCTs. They were instructed to rate the CRC educational materials used in the WhatsApp chatbot regarding different components of HBM, followed by discussions on the reasons for screening uptake and longitudinal adherence, respectively. Inductive coding was used to analyze the interview data to identify the profile of facilitators and barriers for screening uptake and longitudinal adherence.Results The common facilitators for screening uptake and longitudinal adherence were perceived susceptibility, perceived benefits, cue to action and reminders. The unique reason for longitudinal adherence was previous positive experience with health promotion programs. The common barriers to screening uptake and longitudinal adherence were procedural inconvenience and a busy schedule. Different from longitudinal adherence, barriers to screening uptake uniquely included death anxiety and fatalism beliefs. Conclusions There is higher convergence in the facilitators for CRC screening uptake and longitudinal adherence regarding HBM constructs, i.e., perceived susceptibility, perceived benefits, and cue to action. HBM-based interventions can be incorporated in organized CRC screening programs to improve both initial uptake and longitudinal adherence.