The third case in a three-part series, this article chronicles the treatment journey of a 50-year-old male patient who had been diagnosed with left-sided colon cancer in January 2016. After multiple FOLFOX doses, FOLFIRI cycles, and resection, the patient began treatment with regorafenib in July 2020 as a third-line treatment, with the hope that this agent could potentially re-sensitize the tumor to subsequent anti–epidermal growth factor receptor (EGFR) therapy.