Background: We analyzed different methods used to assess the radiological responses of patients undergoing neoadjuvant chemotherapy and metastasectomy treatment for liver metastases associated with colorectal cancer (CRC) by comparing the response evaluation criteria in solid tumors (RECIST) 1.1, the modified RECIST, and the criteria of the European Association for the Study of the Liver (EASL) methods and the histological response obtained after metastasectomy. Objectives: We aimed to determine the optimal radiological method to assess the response of colorectal liver metastases to neoadjuvant chemotherapy. Patients and Methods: We conducted a retrospective study of CRC patients treated for liver metastases who had received neoadjuvant chemotherapy in our hospital between January 2000 and December 2017. We analyzed the agreement between the methods for analyzing the radiological response using the quadratic weighted kappa coefficient (κ). We studied the overall survival and analyzed factors related to survival using the Kaplan-Meier method. We performed multivariate analysis to study the prognostic factors of survival. We analyzed the relationship between the radiological and histological responses using Goodman and Kruskal's gamma (γ). Results: A significant agreement was observed between the modified RECIST and EASL methods (κ = 0.841, P < 0.001). Cox regression multivariate analysis indicated the RECIST 1.1 criteria as an independent prognostic factor (P = 0.03). The γ value showed a significant relationship between the three radiological response methods and histological response. Conclusion: In our study, we showed that using RECIST 1.1 criteria is the ideal radiological analysis method for studying CRC liver metastases treated with neoadjuvant chemotherapy when compared to other methods that are based on functional imaging markers.