The 36-year-old Ferrer, who has been ranked as high as No. 3, has pledged to retire in May.
Also on Tuesday, fifth-seeded Joao Souza of Portugal overcame Argentina's Juan Ignacio Londero 6-3, 6-4.
Seventh seed Dusan Lajovic of Serbia lost to Argentina's Leonardo Mayer 6-3, 7-6 (3).
Aljaz Bedene of Slovenia, a finalist last year, beat local favorite Guido Andreozzi 1-6, 7-6 (5), 6-2.
Spain's Jaume Munar surprised Argentinian Federico Delbonis with a 6-2, 2-6, 6-1 victory.
The third Spaniard to win was Roberto Carballes Baena, who overcame Japan's Taro Daniel 6-1, 6-0.
In an all-Argentine clash, Guido Pella advanced with a 3-6, 6-4, 6-1 win over Francisco Cerundolo.
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