BACKGROUND: Radiotherapy (RT) is an essential treatment for colorectal cancer (CRC), yet the factors influencing radiosensitivity remain unclear. In the quest to enhance the therapeutic efficacy in CRC, the interplay between genetic mutations and RT sensitivity has emerged as a pivotal yet enigmatic area. METHODS: We harness the fidelity of patient-derived organoids (PDOs) to dissect the molecular landscape of radiosensitivity, with a particular emphasis on BRAF RESULTS: Our systematic investigation unveils a profound correlation between BRAF CONCLUSIONS: This study outlines the distinct radiobiological profile of BRAF