You can file the Tax Returns but you will not be allowed any refunds from withholdings or refundable Tax Credits such as Earned Income Credit. The IRS will not issue a refund on Tax returns that are filed more than 3 years from the original due date.
You mentioned above that they have already withheld a certain amount for those Tax Years that your spouse did not file a return. This sounds to me like the IRS has already created Substitute Returns on your wife's behalf. The Substitute Return is created by the IRS with the information that they have about your spouse's income on record. This information is then used to create a return sans Credits, Deductions, Exemptions, etc.
It can be a risky to file those returns because of the possibility of creating more liability. The IRS will not give you a refund for Tax Returns filed more than 3 years late but they will expect to get paid. If filing a Tax Return creates a liability greater than what you have already paid it is a valid debt.
