In 1861 Mallarino was tapped again to serve as Secretary of Foreign Affairs, this time appointed by President Bartolomé Calvo Díaz during the Civil War of 1860–1862. For this reason when Mallarino took office on 1 April 1861 as the 2nd Secretary of Foreign Affairs of the Granadine Confederation he only served until 10 July, when General Mosquera, under whose Administration he had served as Secretary of Foreign Affairs in the past, deposed President Calvo and toppled the Government.