Background: Effective first-line therapy is a key determinant of treatment outcomes and should be selected after considering both clinical factors and biological markers in metastatic colorectal cancer (mCRC). Considering the increased number of cancer patients with old age and their chronic diseases, it is essential to select a therapeutic agent by evaluating the toxicity that may occur due to long-term chemotherapy. This study assessed changes in renal function for 1 year in patients diagnosed with mCRC during chemotherapy and analyzed the factors and effect of each chemotherapy regimen on renal function. Methods: We retrospectively investigated patients with mCRC treated with palliative 1st line chemotherapy at our institution from 2015 to 2020. According to the common 1st line treatment regimen, we divided into 4 groups; FOLFOX/FOLFIRI with bevacizumab/cetuximab. We checked the baseline renal function and 3, 6, 9 and 12 months after the start of chemotherapy. The change in estimated glomerular filtration rate (△eGFR) was calculated as [(eGFR at each time point) - (eGFR at baseline)/(eGFR at baseline) X 100]. The clinical factors such as age, gender, chronic disease, BMI (body mass index), disease status, baseline proteinuria, and 1st line chemotherapy regimen were evaluated. Proteinuria was detected on urine dipstick protein ≥ 1+. Additionally, predictors for ΔeGFR ≤−30% at each time points after therapy initiation were evaluated using multivariate logistic regression analysis. Results: Among 466 mCRC patients, the median eGFR values at baseline was 95.4 ml/min/1.73m². The median eGFR at 6 months after chemotherapy initiation were significantly lower than baseline (88.3 ml/min/1.73m², p < 0.001). As 1 year, patients with more than 30% worsening of renal function was observed in 27.6 % in FOLFIRI + bevacizumab, 26.3 % in FOLFOX + bevacizumab, 6.6 % in FOLFIRI + cetuximab, and 4.7 % in FOLFOX + cetuximab group. The FOLFIRI + bevacizumab was an independent predictor for ΔeGFR ≤−30% at 6 months (odds ratio (OR) 1.94, 95% confidence interval (CI) 1.05-3.47, p = 0.034) along with old age (≥ 65 years, OR 2.18, 95% CI 1.29-3.68, p = 0.004) and BMI (p = 0.012). Additionally, FOLFIRI + bevacizumab regimen causes more proteinuria (46.4%) than other chemotherapy regimens. Conclusions: Deterioration of renal function was more common with FOLFIRI + bevacizumab than other combination regimen. Old age, BMI were also associated decreasing eGFR. These results will be helpful to be suggested as important consideration when selecting the 1st line chemotherapy regimen for mCRC.