: Colorectal cancer (CRC) is one of the major epidemiological oncological confronts with established risk factors, including male sex. Still, CRC is reported among the leading malignancies in the female population. The necessity for possible, easily accessible prognostic factors is required to improve patient outcomes. This study aimed to assess sex-related differences in nine-month four-stage CRC results of palliative systemic therapy. : A total of 67 patients (39 males) with a median age of 70 (64-76) years were referred for first-line palliative chemotherapy due to end-stage colorectal cancer diagnosis. The CRC advancement was evaluated by computed tomography (CT) before and 9 months after chemotherapy. The demographical and clinical characteristics were evaluated for nine-month therapy outcomes, including mortality risk and CT scan results. : The nine-month mortality risk in female and male groups was indifferent, reaching 21% (6 patients) and 21% (8 patients), respectively ( = 0.935). Among survivors, therapy response was observed in 6 (21%) female and 20 (51%) male patients ( = 0.056). In multivariable analysis, the male sex (OR: 3.91, 95% CI: 1.09-14.05, = 0.037) and RDW (OR: 0.61, 95% CI: 0.42-0.88, = 0.008) were found to be significant for disease response to systemic therapy based on CT scan results. The ROC curve for predictive role yields a sensitivity of 71.1%, specificity of 57.8%, and an area under the curve (AUC) of 0.726. : Our analysis points out the possible favorable role of the male sex on nine-month systemic therapy response in palliative CRC. The RDW-CV can be regarded as a possible indicator of chemotherapy response in colorectal cancer. The mortality risk within 9 months of systemic therapy is comparable between males and females.