• written informed consent to study procedures;

• age ≥ 18 years;

• histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma;

• radiological evidence of metastatic disease;

• evidence of measurable disease according to RECIST 1.1 criteria;

• presence of BRAF V600E mutation in tumor tissue (primary CRC and/or related metastasis) as previously determined by a local assay at any time prior to screening (only PCR and NGS-based local assays results will be acceptable);

• disease progression while on treatment with EC received in 2nd line setting

‣ EC administered after disease relapse during treatment or within 6 months following adjuvant therapy will be second line;

⁃ maintenance therapy given in the metastatic setting after a first line doublet or triplet chemotherapy will not be considered a separate regimen;

• best response to previous treatment with EC: CR, PR or SD lasting for at least 3 months.

• patient fit for a subsequent treatment line with FOLFIRI. Patients exposed to irinotecan and fluoropyrimidines during previous line for metastatic disease are eligible, provided that the patient has recovered from G3 toxicity;

• life expectancy ≥ 3 months;

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤1.

• Adequate bone marrow function at screening:

‣ Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L;

⁃ Platelets ≥ 100 × 10\^9/L;

⁃ Hemoglobin ≥ 9.0 g/dL;

⁃ Note: Transfusions will be allowed to achieve this. Transfusions will be permitted provided that the patient has not received more than 2 units red blood cells in the prior 4 weeks to achieve this criteria.

• Adequate renal function at screening: serum creatinine ≤ 1.5 × upper limit of normal (ULN), or calculated by Cockroft-Gault formula, or directly measured creatinine clearance ≥ 50 mL/min at screening.

• Adequate hepatic function at screening:

‣ serum total bilirubin ≤ 1.5 × ULN;

⁃ alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN in presence of liver metastases.

• Adequate cardiac function characterized by the following at screening: QT interval corrected for heart rate using Fridericia's formula (QTcF) value ≤480 msec.

• Availability of treatment-naïve, archival FFPE tumor tissue sample.

• Ability to take oral medications.

• Male subjects with female partners of childbearing potential must be willing to use adequate contraception, starting with the first dose of study therapy through 180 days after the last dose of treatment. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

• Women of childbearing potential must have a negative blood or urine pregnancy test at the baseline visit.

• Female subjects of childbearing potential must be willing to use an adequate method of contraception, for the course of the study starting with the first dose of study therapy through 180 days after the last dose of treatment. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

• Will and ability to comply with the protocol.