Colorectal cancer (CRC), a highly prevalent malignant tumor worldwide, has shown a continuously increasing incidence, particularly with the rise of early-onset CRC in young populations. Neoadjuvant therapy, as an important strategy for locally advanced CRC, shows significant potential to downstage tumors, improve radical surgical cure rates, and enhance prognosis. In this paper, a 39-year-old male patient with sigmoid colon adenocarcinoma at clinical stage cT_4aN_2aM₀ (stage Ⅲ_C) is reported. Genetic testing revealed a mutation in the oncogene KRAS (G13D) and microsatellite stability (MSS). The patient also had significantly elevated carcinoembryonic antigen (CEA), lymph node metastasis, and suspected pelvic implant nodules, with a high risk of invasiveness and potential peritoneal metastasis. Because he had a refractory subtype of CRC with poor response to traditional immunotherapy, the patient was treated with neoadjuvant therapy, comprising CapeOx regimen (capecitabine+oxaliplatin), followed sequentially by sluzumab; after 6 treatment cycles, the tumor shrank significantly, and laparoscopic radical sigmoid colon resection was successfully performed, with no residual (ypT₀N₀) confirmed by postoperative pathology. This case suggests that for patients with KRAS-mutated MSS CRC resistant to traditional immunotherapy, a combination of CapeOx chemotherapy followed by programmed death-1 (PD-1) inhibitors may induce a deep pathological response and provide translational treatment opportunities for locally advanced patients. However, the universality and long-term benefits of this treatment regimen still require further longitudinal studies and clinical follow-up.